The formation and stabilization of colloidal dispersion systems have been extensively studied. The stability of these systems can be enhanced by adding a surface active agent or surfactant to modify the interfacial interactions between the components of the system. In selecting the surfactant for such systems, the surfactant's hydrophilic-lipophilic balance (HLB) is traditionally is considered. The HLB scale is based on the relative percentage of hydrophilic to lipophilic groups in the surfactant molecule. For example, an Oil-in-Water (O/W) emulsion would require a high HLB value (e.g., 10-18) to solubilize the molecules in water. The HLB scale by itself, however, fails to indicate whether a specific surfactant will be effective as a delivery agent for active ingredients. In such situations, where the colloidal dispersion system includes active ingredients, the structure of the surfactant molecule should also be considered.
When present, the micelles in a colloidal dispersion system exist in dynamic equilibrium where the rate at which surfactants exchange (or move) between the continuous phase and the micelle phase varies depending on the structure of the surfactant molecule. This rate, in turn, affects the active ingredient's ability to diffuse into/out of the micelles. Without being limited by theory, it is believed that the efficacy of an active ingredient is linked to the active ingredient's ability to diffuse out of the micelles; more specifically, it is believed that the size of hydrophobic chains (for water in oil systems) or hydrophilic chains (for oil in water systems) of surfactants control the ability of active-ingredient, solubilized in a micelle's core, to diffuse in or out of the micelle.
US Patent Publication 2012/0003163 A1 teaches that poloxamers negatively affect the bioavailability of essential oils used as actives ingredients. A nonlimiting theory for this negative effect relates to the number of block units in such poloxamers and the ratio of the polyethylene oxide (PEO) and polypropylene oxide (PPO) blocks, namely poloxamers having higher numbers of PPO blocks and a copolymer length of greater than 30 units (blocks) produces a strong (or increases strength of the) association between the PPO blocks and the active ingredient, locking active ingredient in the core of the micelle and reducing bioavailability.
Because of such negative effects on active ingredient bioavailability, anionic surfactants such as sodium lauryl sulfate (SLS) are typically substituted for poloxamers. Such anionic surfactants have little effect on active ingredient bioavailability as they function as dispersants and not emulsifiers for the essential oils, which allow them to have less of an effect on the bioavailability. In certain situations, however, the use of SLS may be limited in view of its skin/mucosal irritating properties. Poloxamers, on the other hand, are not irritating to skin or mucosal surfaces. There is, therefore, still a need for poloxamers which increase or otherwise improve the bioavailability of active ingredients like the essential oils.
The present inventors have found that PEO-PPO block copolymers having a ratio of PEO and PPO blocks greater than 4 to 1 and a copolymer length less than 30 units reduce the association between the PPO blocks and active ingredients, improving bioavailability.